Using cluster analysis to explore COVID-19 vaccine booster hesitancy by levels of medical mistrust in fully vaccinated US adults

Abstract Background Underlying causes of vaccine hesitancy could significantly affect successful uptake of the SARS-CoV2 vaccine booster doses during new waves of COVID-19. Booster rates among US adults are far below what is needed for immunity, but little is known about booster hesitancy among fully vaccinated adults and whether medical mistrust exacerbates barriers to uptake. Methods A cross-sectional survey was completed among 119 adults in Philadelphia, PA who reported having received the primary SARS-CoV2 vaccine series but not a booster dose. Using the LaVeist Medical Mistrust (MM) Index, a k-means cluster analysis showed two clusters (Low MM, High MM) and differences in attitudes and perceptions about COVID-19 booster vaccines were assessed using F-tests. Results Respondents were 62% Black and female; mean age was 41; 46% reported earning less than $25,000 and 53% had a high school education or less. Overall intention to get boosted was low (mean 3.3 on 0-10 scale). Differences in COVID-19 booster perceptions between those with High (n = 56) vs. Low (n = 59) MM were found, independent of any demographic differences. Most statements (7/10) related to reasons to not be boosted were significant, with those with High MM indicating more concern about feeling sick from the vaccine (F=-3.91, p≤ .001), beliefs that boosters are ineffective for vaccinated people (F= −3.46, p≤ .001), and long-term side effect worries (F=-4.34, p≤ .001). Those with High MM were also more concerned about the adverse effects of the vaccine (F=-2.48, p=.02), but were more likely to trust getting information from doctors or healthcare providers (F= −2.25, p=.03). Conclusions Results indicate that medical mistrust is an important independent construct when understanding current COVID-19 booster hesitancy. While much work has looked at demographic differences to explain vaccine hesitancy, these results suggest that further research into understanding and addressing medical mistrust could be important for implementing interventions to increase booster rates.


Introduction
Vaccine hesitancy has become an increasing threat to public health, most recently manifested during the cOViD-19 pandemic.in the Us, vaccination rates indicated certain groups were less likely to be vaccinated, including Black/african americans, younger adults, white men with less than a college education, and those with a conservative ideology [1][2][3][4][5].While the Us had a close to 70% overall vaccination rate (completing the primary series), the emergence of cOViD-19 variants has threatened the progress made with vaccinations [6].For example, the Omicron variant resulted in record-high cOViD-19 case counts regardless of vaccination status [6].however, booster shot doses in the fully vaccinated population can bolster waning immunity and protect vaccinated individuals from cOViD-19 variants.this would be helpful for saRs-coV-2 variants such as Omicron or the new subvariant of Omicron, JN.1, which now makes up over 60% of new Us cOViD cases [7].since January 2022, the Us centers for Disease control and Prevention (cDc) recommended an mRNa booster dose after receiving the primary vaccination series, which has been shown to decrease transmission, as well as hospitalization and emergency room visits [8,9].however, only 17% of the total Us population 5 years of age or older has received a booster [6]. in Philadelphia, where this research occurred, there are even lower rates of booster uptake among Black and hispanic residents [10,11].the divide between those who are booster eligible-those who have already received the primary vaccination seriesand those who are boosted must be narrowed to adequately protect the public from future waves of the saRs-coV-2 virus.
Understanding the drivers of booster hesitancy can help public health professionals intervene to encourage cOViD-19 booster uptake.But getting people to accept vaccination is a complex decision, especially a vaccine that has been the subject of significant mis/ disinformation [6,[10][11][12][13][14].While work has been done to understand barriers to uptake of the primary cOViD-19 vaccine, it is unclear what is driving low rates of booster uptake in the Us, since those eligible have already made the decision to get the primary vaccine series.studies that have looked at cOViD-19 booster acceptance and/or hesitancy have been done among non-Us populations using web-based surveys, which limits the generalizability to the Us adult population [11][12][13][14][15][16]. the few that have looked at Us adults have shown that just over 20% of fully vaccinated U.s. adults are unsure or hesitant to get a recommended booster dose [17,18].concerns include negative experiences with side effects from prior cOViD-19 vaccine doses, uncertainties about booster side effects, worry about chronic health issues or allergic reactions, and no mention of need for boosters when getting the primary vaccine series [19].
One topic that has yet to be explored as a potential barrier to cOViD-19 booster uptake is medical mistrust.Defined as the lack of trust or suspicion of any medical organizations, including health providers and treatment themselves [20,21], medical mistrust is rooted in the historical and current mistreatment of those socially and economically marginalized populations.it has been found to be an important construct connected to health behaviour, medical decision making and patient-provider communication [20,21].Mistrust of research, pharmaceutical companies and governments in general has also specifically been associated with the saRs-coV-2 pandemic.in the Us, it has been connected to the distrust of scientific information about transmission, need for protective measures like mask wearing and social distancing, and the vaccine, where many people believed it was simply another form of experimentation [20,21].Mistrust also affected initial vaccine uptake [21] and facilitated the relationship between conspiracy beliefs and vaccine hesitancy [21].
inherently, medical mistrust is often connected to race/ethnicity, particularly through evidence of experimentation on racial and ethnic minorities such as the tuskegee syphilis study between 1932 and 1972 [20].this historical evidence, along with documented lower levels of health literacy [22]; sociocultural factors such as media representation, racial discrimination and community influences [22]; and less or inadequate health insurance coverage [22], as well as specific attitudes or fears about how they might be treated in the healthcare system, all contribute to a distrust by racial and ethnic minorities [22].these feelings thus extend beyond the history of the tuskegee experiment [22], reinforced by contemporary discriminatory practices in the healthcare system [22] that affect individual level participation in healthcare decision making, but also trust of system level communication, such as widely disseminated information and messages about cOViD-19 booster vaccinations [23,24].
importantly, there is evidence that medical mistrust has been a barrier to cOViD-19 vaccination uptake especially among minoritized populations, including whether someone received more than one [25].Bogart et al. found that 97% of Black or african american participants expressed mistrust of the cOViD-19 vaccine [26].this is not surprising, as Black americans have shown to be significantly more likely to report 'no' or 'not sure' to questions about willingness to uptake a vaccine when compared to White counterparts.For cOViD-19 specifically, many Black individuals feared that the rapid development and promotion of the vaccine in their communities, especially in a sociopolitical climate they perceived to be hostile, was evidence to distrust the vaccine and other communication about cOViD-19 mitigation efforts [27].studies in 2021 and 2023 found that combined perceived discrimination experienced by Black americans every day fuels medical mistrust and thus results in a lower odds of having the cOViD-19 vaccine compared to those that do not experience discrimination [27,28].When the level of suspicion of the cOViD-19 vaccine is high, evidence suggests this outweighs any other potential facilitator, such as it being a social responsibility or a way to keep oneself from being sick [29].Whether that holds true for cOViD-19 booster shots is unknown.
thus, medical mistrust may be an important construct in understanding why previously vaccinated adults have not made the decision to have a cOViD-19 booster shot, especially as cOViD-19 resurges in communities [27][28][29][30].But its impact on barriers and facilitators is poorly understood.this study aims to understand whether medical mistrust and its association with barriers and facilitators could help explain the decision-making process to receive a cOViD-19 booster.the main research question is whether those with more medical mistrust will report more barriers and fewer facilitators to receiving a cOViD-19 booster compared to those with lower levels of medical mistrust.this exploratory research could be used to inform future interventions that aim to address medical mistrust and encourage proper prevention strategiessuch as booster uptake-in a future disease outbreak in the United states.

Methods
these analyses utilized data from a quantitative survey that was part of a mixed-methods study to explore experiences with cOViD-19 vaccination, understand drivers of intent to receive a booster dose and elucidate psychosocial, experiential and structural barriers to receipt of a cOViD-19 booster dose.the purpose of this formative work was to provide data to inform the development of a community-based cOViD-19 booster communication campaign.the cross-sectional survey was conducted among residents of Philadelphia, Pa who reported receiving their primary vaccinations but not their booster shots.Data were collected from March through May 2023.
Participants were recruited a number of ways through convenience sampling strategies, including in person at community organizations across the city-at a major safety-net hospital-at planned events or locations and online.at in-person events, staff asked people if they would be interested in participating and if interested, screened to determine eligibility.Participants could take the survey either on an iPad or their own device or on paper as self-administered or read to them by study staff.Online recruitment was completed by asking community organizations to post information to their social media accounts, as well as through posted flyers or recruitment cards that were available at various city locations.all materials had a QR code, URl and phone number.Participants could scan or click on the link, which would take them to a secure eligibility and survey link, or, if they preferred, could call study staff and complete the survey over the phone.surveys utilized Qualtrics, the secure online survey software [31].all participants provided written informed consent and if completed online, iP addresses were checked to ensure it was located in Philadelphia.
Data collection occurred between December 2022 and May 2023.all participants received a $15 gift card upon completion.temple University's institutional Review Board reviewed and approved this study (#29430).

Measures
the survey instrument developed by the authors used both validated measures as well as study-specific items based on findings from qualitative interviews [32] and previous research on cOViD-19 vaccine hesitancy [33]. it consisted of sociodemographic questions and sections related to cOViD-19 experience and knowledge, vaccine acceptance and literacy, information sources and trust, willingness to get the booster, beliefs about the booster, reasons not to get the booster and barriers to getting the booster.all sections were presented in blocks of statements for respondents to agree or disagree with on a zero to 10 scale (zero = highly disagree, 10 = highly agree).
the following validated scales were used;  [35].these items measure how much a respondent believes in conspiracies (e.g.'important things happen in the world the public is never informed about').
• Medical Mistrust: laVeist et al. 's seven item Medical Mistrust index was used to measure levels of mistrust [36].items assess how much a respondents believes that institutions may or may not be trustworthy (e.g.'healthcare organizations have sometimes done harmful experiments on patients without their knowledge').
Other survey items were informed by the centers for Disease control and Prevention survey items on barriers to getting the cOViD-19 vaccine [34], the Kaiser Family Foundation cOViD-19 Vaccine Monitor survey from July 2022 [28], as well as the study team's previous work on cOViD-19 vaccine hesitancy [33] and formative qualitative interviews with those who had been vaccinated but not boosted [32].all sections were presented in blocks of statements for respondents to agree or disagree with on a zero to 10 scale (zero = highly disagree, 10 = highly age).these sections included: Finally, one item measured participants' selfdescribed willingness to get the cOViD-19 booster, in line with the Diffusion of innovation theory's adopter categories [37].since none of the respondents had yet been boosted, categories included: early Majority ('i plan to get boosted but just haven't gotten around to it'), late Majority ('i will get the booster shot if people i trust tell me that i should get it') and laggards ('i'd rather wait to get the booster shot until everyone else has gotten it').a 'refuser'category was also added because of preliminary work that indicated a number of those would not get the booster under any circumstances [32], despite having already been vaccinated.this was operationalized with two statements ('i don't want to get the booster shot because i'm not really sure i need it' and 'i will never get the booster shot').

Analytic plan
to examine associations between our constructs of interest, we performed a k-means cluster analysis using items from the laVeist Medical Mistrust index (MM) scale [36].a non-hierarchical method is used in the k-means approach to clustering to discern latent subgroups within a sample.individual cases are then assigned to a predetermined number of clusters according to their proximity to the nearest centroid (mean) of constituent items [38].this is then performed iteratively until the desired number of clusters is produced.Four cases were excluded because of missing data, reducing the total sample size from 119 participants to n = 115.From this, a two-cluster solution was found (low MM, n = 59 and high MM, n = 56).Once a cluster solution was found, the associations between membership in one of the two clusters and survey items were assessed using F-tests to test for potential differences in perceptions of and attitudes about cOViD-19 booster vaccines, including perceived booster barriers and facilitators.an alpha value of 0.05 was used to determine statistical significance.chi square tests were used to compare demographics between clusters.all analyses were done with sPss v. 28.

Results
Differences between clusters based on their constituent items were analyzed to create definitions for both clusters.table 1 reports the means for each item delineated by cluster.We use the terms low Medical Mistrust (MM) for cluster 1 and high Medical Mistrust (MM) for cluster 2 to apply common nomenclature to denote how segments differed by the study variables.

Sample demographics
Overall, a majority of the sample was african american/ Black (62.1%), finished high school or below (53.4%), had health insurance (92.1%), identified as Democrat (53.5%) and were female (61.9%).almost half made less than $24,999 a year in income (46.1%).average age was 41.43 years.table 2 presents a summary of demographics by total sample and by cluster along with other variables of interest.No significant differences were observed between clusters on any demographic variables.The range of 0-10, 0 = completely disagree to 10 = completely agree.

Diffusion of innovation adopter categories
Distributions of adopter categories were found to be significantly different between clusters (p = 0.03), with the low MM cluster more likely to say the still plan to get the booster 'but just haven't gotten around to it' (i.e.'early majority') (28.8% vs. 17.9%).those with high MM were more likely to say that they would 'never get the booster' (i.e.'refuser') (28.6% vs.

Booster barriers/refusal
seven out of ten items in this section were found to be significant.those with high medical mistrust were more likely to agree with the following statements: 'i had a friend or family member who had a bad reaction when they got the booster so i don't want to get one' , (M = 3.

Vaccine acceptance
there was one significant item found in this section where those with high MM were more likely to say 'i'm concerned about the adverse effects of vaccines' , (M = 7.29 vs. M = 5.97; F(113)= −2.48; p = 0.02).

Information sources
Finally, there was one significant item in who the groups trusted with cOViD information.those with high MM were more trusting of doctors or other health care providers than those with low MM (M = 7.21 vs. M = 5.86; F(113)=-2.25;p = 0.03).
the impact of medical mistrust on cOViD-19 booster decision making in those who have completed their primary vaccination series has not been previously documented in Us populations.the objective of this formative work was to characterize booster hesitancy in a cross-sectional convenience sample of adults living in Philadelphia who had previously been vaccinated but not boosted and assess the impact of medical mistrust on their perceptions about the barriers and facilitators to being boosted.Results identified two distinct cluster groups using the Medical Mistrust index which did not differ by demographic characteristics, indicating it is a unique, independent variable important to understanding potential booster hesitancy in the population.this is important as other work has primarily used demographic descriptors to compare booster hesitancy across populations [17,39].thus, medical mistrust could be a helpful construct when thinking about developing future interventions during an ongoing pandemic [20,21,[25][26][27].
Finding suggest that medical mistrust primarily affects perceived reasons to not get a cOViD-19 booster.this suggests that aside from other social and structural barriers that americans might face in receiving a booster, there are significant intrapersonal barriers that impede uptake, even among those who have received their primary vaccinations.those with high MM were significantly more likely to agree with most of the reasons to not get a booster, including not thinking the vaccine works, worry about similar side effects to the primary vaccination, belief that others had had negative side effects from the booster, and wanting to wait to see 'what happens' .this finding is important within the context of prior studies on vaccination refusal, where those who perceived stronger barriers were less likely to receive a vaccine [40][41][42][43].
this suggests that people who are less trusting of the medial system are fearful of getting the booster shot, do not believe in the booster shot as an effective way to combat cOViD-19, do not trust or are concerned about the safety of the booster shot, or simply do not want to get the booster shot now that they have completed their primary vaccination series.clearly, even though both clusters had not been boosted, mistrust of the medical system has an evident impact on perceptions of why one would or would not get boosted.
interestingly, reasons to get the booster were not statistically different by the cluster groups.this may be driven by the amount of mis/disinformation available on cOViD-19 generally, which often amplifies the vaccine's negative side effects.Betsch et al. found that even a short exposure to content critical of any vaccine leads to increased perceived risk and decreased intention of being vaccinated [44].information about the cOViD-19 pandemic has largely played out on social media, a first in public health.Despite most participants indicating they do not 'trust' social media for cOViD-19 information, its ability to quickly spread mis/ disinformation using first-person accounts and imagery can have an important impact on public thinking [45].this result is similar to other findings about trust of information sources, with those saying they do trust social media being also more likely to not believe science-based sources and to attenuate their perceived risk of negative cOViD-19 effects [46,47].this, when coupled with medical mistrust, may fuel hesitancy and impact beliefs about the cOViD-19 booster, counteracting any positive information about why one should be boosted [21,48,49].however, participants with higher levels of medical mistrust also said they were more likely to trust their doctor or healthcare provider for cOViD-19 booster information.this disconnect between having trust of a personal healthcare provider compared to the larger healthcare system, has been seen in other research.in fact, past research has established that the quality of patient-provider relationships can moderate the relationship between greater medical mistrust and healthcare engagement [25].this is important in that it may provide a useful intervention strategy to get booster information to those who have more hesitancy, and has already been an established correlate to cOViD-19 primary vaccination uptake [50].this finding could be leveraged in interventions aimed at increasing booster uptake.
this study also highlights the role of Diffusion of innovation and concern about the pandemic (and prevention of illness) in booster uptake.those with higher levels of medical mistrust were more likely to fall in the 'laggard' or 'refuser' adopter categories, despite the finding that this group also reported reading more information about the boosters and not having significantly different levels of vaccine acceptance than those with lower medical mistrust.this further highlights the potential impact medical mistrust has on the booster decision.since 'laggard' adopters are more likely to trust information from those around them (i.e.personal doctors, friends, family, religious leaders) [51], if one opinion leader is not supportive of the decision or also has higher levels of medical mistrust, positive information may be less likely to be diffused in communities.this is supported by some previous work in the context of cOViD-19 vaccination [52].even though they may be receiving information and understand why the booster is needed, mistrust of the healthcare system by both themselves and those around them may negate this information [52,53].as a result, future strategies to diffuse or promote the cOViD-19 booster must take into consideration the already existing fear and mistrust that many communities have towards the medical system and acknowledge the importance of diffusing to whole communities, rather than just individuals.these findings suggest that using community-based approaches that use trusted messengers to talk about the cOViD-19 boosters are more likely to diffuse information that is trusted.Utilizing existing community-based organizations or enlisting the help of community leaders could be an important strategy to address fears and mistrust of the medical system that may be embedded in perceived barriers and reasons to refuse the booster.these types of interventions were effective at reaching vulnerable populations with the primary vaccination series [54,55], and could serve as a model for encouraging uptake of the cOViD-19 boosters.
it is clear, especially among barriers and reasons for refusal of the booster, that medical mistrust may serve as a mediator in the decision-making process of vaccine uptake.these findings can be used as a guide on how best to move individuals towards booster uptake when they have fear, mistrust and skepticism towards the medical system.however, though work by carico et al. suggests that people will participate in preventative behaviours if they perceive it to be a large threat to their health, this is certainly not enough; the threat posed by the solution to the problem itself (the booster as a solution to cOViD-19) must be addressed as well [56].acknowledging medical mistrust, while also promoting the booster as safe and effective, and using trusted sources of information from their community, may potentially have an effect on improving uptake of the cOViD-19 booster.since this study did not sample those who had been boosted to compare levels of mistrust across groups, future research should further explore the role of medical mistrust as a mediator for booster uptake.if it is found that medical mistrust is indeed lower in those who have been boosted, an intervention aimed at increasing trust to see if higher booster rates can be achieved would be warranted.
there are some limitations to this study.First, due to the nature of cross-sectional data from a convenience sample, temporality inferences could not be made and data may not be representative of a broader population.additionally, the survey relies on self-reported data, so social desirability bias should be considered when evaluating results.On a larger scale, results may not be generalizable to the entire Us population, as the study was conducted only in Philadelphia and among people who have received the entire primary vaccination series.conclusions may not be able to be made for others in different geographic areas or those who have not finished their primary vaccination series.More importantly, those who are in different geographic areas may perceive the threat of cOViD-19 differently, receive their information from different sources, have differing levels of vaccine literacy and have different relationships with the medical system (and thus differing levels of medical mistrust).the relatively small sample size also limits the possibility of using alternate statistical models and/or controlling for covariates.While the study sample was adequate for completing the formative analyses presented in this study, it may have resulted in less valid estimates compared to those that could be found within a larger sample size.Finally, because we only sampled those who had not been boosted, our ability to make conclusions from our findings is limited to this population.

Conclusion
Understanding how to best balance medical mistrust and the threat from cOViD-19 can better inform community-based interventions to improve future pandemic response in the Us.Findings from this work indicate that better addressing medical mistrust in interventions with trusted messengers will be important to increasing the rate of booster acceptance in populations that may have higher levels of medical mistrust.h.G.K.s., c.l., a.h., M.K., a.M.R., e.K., s.M., s.V., i.W.s: critical revision of the manuscript.all authors approved the final draft for publication of this manuscript.

Table 1 .
chi square p-values and group distributions for Diffusion of innovation adopter categories are reported in table 3. Means, standard deviations, F-values, p-values and cohen's d are reported in table4for all survey items in survey sections where there was at least one significant differences between two groups on clustering variables.

Table 3 .
differences between clusters on diffusion of innovation.

Table 4 .
differences between clusters on other perceptual items.